There are numerous patents and publications which describe various lateral-flow or immunochromatographic test kits and methods for the detection of the presence or concentration of chemical residues or analytes or classes thereof from liquid samples. One publication includes xe2x80x9cA SHORT GUIDExe2x80x94developing Immunochromatographic Test Stripsxe2x80x9d by Millipore Corporation, Bedford, Mass., while U.S. patents would include U.S. Pat. No. 4,703,017, issued Oct. 27, 1987; U.S. Pat. No. 5,591,645, issued Jan. 7, 1997; U.S. Pat. No. 5,266,497, issued Nov. 30, 1993; U.S. Pat. No 4,999,285, issued Mar. 12, 1991; U.S. Pat. No. 5,238,652 issued Aug. 24, 1993; and U.S. Pat. No. 5,622,871, issued Aug. 22, 1997 (all hereby incorporated by reference).
U.S. Pat. No. 5,622,871 describes analytical test devices for biological fluids which include elongated, rectangular, hollow casings to contain a test strip, and which casings have an aperture to permit visual observation of the test results on the test strip. The casings include a protective, removable cap to protect and enclose the application end of the casing. The internal constructional details of the housing are not a significant feature of the invention, but are employed to provide a housing for the particular test strip (column 12, lines 20-26).
It is desired to provide a new and improved analyte test device and method based on test strips in which the housing of the test strip is designed to promote the absorption, flow and efficiency of the test device and the tests carried out.
The invention relates to an analyte or chemical residue test device and method employing a lateral-flow test strip for the detection of the analyte or residue within a housing and a method therefor.
The invention comprises an analyte test device for detecting, in the general horizontal position, an analyte in a liquid sample by capillary lateral flow in an inmunochromatographic test strip, which device comprises an elongated housing defining an elongated strip cavity having a one open application aperture at one end and having another end, the cavity adapted to receive and hold a test strip therein, and having a transparent top cover section, to permit the observation of test results on the test strip, the housing characterized by an enlarged application cavity extending outwardly from the top cover and having or adapted to have an open end at the application end. The test device includes a test strip positioned in the strip cavity.
The test strip comprises a support strip with a plurality of sequential, contacting, liquid-sample, permeable zones extending from the first to the second ends, which zones permit the lateral capillary flow of the liquid sample from the first to the second end. The zones include a sample-absorbing and filtering zone composed of an expandable, porous, compressed-material layer which moves, on contact with the liquid sample, between a nonexpanded state and an expanded state on absorption of a preselected amount of the liquid sample, and a releasing zone having a mobile-phase layer thereon with a receptor for the analyte of the liquid sample thereon, typically a visible area, for example, of colored beads. The zones include also a reaction zone having at least one stationary-layer analyte reference or test line, or generally a test and a separate control line thereon for observation, to detect the presence of analytes in the liquid sample, and optionally a disposal zone of a layer of liquid-sample absorbent material for the liquid sample and to induce capillary flow to the second end. The sample-absorbing zone with the compressed material layer is positioned adjacent the application cavity, the compressed-material layer and the application cavity designed to provide the compressed-material layer to absorb a selected amount of liquid sample to be tested and sufficient to carry out the test and to expand from a dry, nonexpanded to a wet, expanded state, and to provide for the said material layer in the wet, expanded state to fill substantially the application cavity and to cause sufficient pressure on the housing walls of the expansion cavity to drive capillary flow of the liquid sample toward the disposal zone in said strip in a selected time period and to restrict flow of the liquid sample in the application cavity to a selected volume, when the open application end of the test device is inserted into a liquid to obtain the liquid sample.
In the invention, one preferred embodiment is the employment of a housing, such as a one-piece, integral, injection-molded, all-transparent, plastic material, with the plastic material selected or designed to be subject to incubator temperatures of 50xc2x0 C. or more for incubation times; for example, of 2 to 10-15 minutes, depending on the particular test.
The preferred embodiment includes a generally toothbrush-type housing shape, with the enlarged, generally rectangular, toothbrush-type head at the open application end of the housing, with a dry, inert, porous, expandable, liquid-permeable, absorbing material in a generally rectangular layer as an absorbing zone in the test strip; for example, of cellulose or nitrocellulose, positioned beneath the open bottom of the application cavity or chamber. The absorbing layer on contact, such as immersion of the application end of the housing of the test device in a liquid, will absorb a preselected amount of the liquid sample required for the test. The absorbing-layer material will expand; for example, in 1 to 30 seconds, to fill or substantially fill the expansion cavity and contact the surrounding walls of the expansion-cavity housing, to cause sufficient pressure within the expansion cavity and in the expanded state of the material to drive capillary flow laterally in the underlying test strip toward the end of the elongated housing where the test strip is positioned. Thus, proper selection and dimensioning of the expansion cavity and underlying absorbing-layer material which generally mimics two dimensions of the expansion cavity, permits absorbing and filtering of the selected amount of liquid sample for the test strip, and aids in driving the lateral flow of the liquid sample in the test strip in the housing toward the end of the test strip; for example, the disposal zone, to receive the liquid sample where employed. If the absorbing layer does not expand sufficiently to fill or substantially fill the expansion cavity, then lateral or capillary flow rates and times are unsatisfactory; that is, flow rate too slow and time period too long. Where the absorbing layer is used in excess, then excess pressure occurs in the expansion cavity, and the expanded absorbing layer tends to retard the desired lateral flow of the liquid sample.
The housing with the toothbrush-shaped design may comprise a separate, injection-molded housing with an optional end cover, to protect the exposed application end before sampling and after sampling, and in the incubation chamber, to prevent cross-contamination from other sources. The test device with the molded housing enables the user to handle the handle end of the housing and to obtain a liquid sample merely by dipping the open application cavity into a liquid.
The housing also may comprise a toothbrush-shaped design, wherein the expansion cavity is formed in a plastic, usually transparent, blister-type package which is sealed against a flat support, such as a paper strip or another plastic strip, and which encompasses within the blister package the selected test strip. The blister package includes a removable seal strip at the one application end of the enclosed test strip, for peeling or removal prior to use and for the introduction of a selected volume of the liquid to the application-absorbing zone of the test strip while in the blister package. The blister package with the liquid sample and test strip may be incubated in the incubator and the test results observed or read.
In a further embodiment, it has been discovered to be desirable to provide one or more apertures in the housing which defines the expansion cavity, to permit the time-controlled and more rapid absorbing of the liquid sample into the absorbing material for more efficient absorption and to reduce absorption time of the liquid sample. In particular, one or more apertures should be placed on the top cover or surface of the expansion-cavity housing, particularly of the molded housing, rather than on the sides, so that entrapped air, after immersion, will be discharged from the expansion cavity, as the absorbing layer expands into the wet, absorbing, expanded state. While a flat, rectangular strip of absorbing material is shown with a generally rectangular expansion cavity which mimics and provides for the expanded, rectangular strip of the absorbing zone, it is recognized that the size, material, dimensions and shape of the absorbing material and the shape or form of the expansion cavity may vary in the practice of the invention. Typically the open bottom of the expansion cavity is directly above the absorbing layer and usually of about the same width and length dimensions, to permit expansion without restriction of the absorption layer into the expansion cavity.
While a fully transparent top cover is desirable to enclose the test strip and observe or read the test results on the test strip, it is recognized that the top cover may be open or have an aperture to view the test results, or only a section of the top cover be transparent to view the test results, or where applicable, the housing may be modified, so that the test results may be determined by optical or electronic instrument means.
The test device may be packaged for use in a blister-type package or employ a fixed or slidable protective cap at the application end, to protect the test device from contamination prior to use and to protect the test device after contact with the liquid sample and in the incubator (where required in the test), to protect against cross-contamination. The protective cap can be removable and enclose totally the application end of the housing, or merely be slidably extended outwardly from the application end between a retracted use position and extended, protective, closed position.
The test device employs a test strip selected to detect the presence or concentration of selected analytes or residues, either a single residue or classes thereof, and visually by reference of a reaction reference zone or reference line in the test strip which may be observed or measured. Usually, a control zone or line is spaced apart slightly downstream from the reference zone or lines for control purposes. The housing of the test device is applicable to a wide variety of presently employed or described test strips which are based on lateral flow or capillary flow, regardless of the nature of the particular analyte-residue test, provided only that the application or liquid contact portion of the test strip requires or uses a filtering absorbing material which moves by liquid-sample contact between a nonexpanded and an expanded state at or toward the one application end of the test device. Typically, the test strip has a support and includes, on one surfaces, a plurality of contacting, liquid-permeable, sequential zones or sections with a stationary zone, a mobile zone and, optionally, a disposal zone. The test device is particularly useful in connection with the liquid sample comprising a biological fluid; for example, urine; blood; or milk, and in the detection of antibiotics, like beta lactams or toxins, viruses and the like; however, the test device may employ one or more test strips directed to a variety of tests.
Where applicable, the test device is employed in combination with an incubator, such as a portable, electrically heated incubator with an incubation chamber which may be dimensioned to receive the test-device housing snugly therein for heating for a selected incubator time; for example, 55 to 65xc2x0 C., and for a period of 1 to 10-15 minutes. The test device and incubator also include a timer, so that the incubation period may be timed by a user.
In operation, the test device with a protective covering or cap has the cover or cap removed and the application end contacted with a liquid to be tested, such as by immersion or a liquid sample pipetted into the application end for 1 to 10 seconds and then removed. The absorbing material is allowed to expand within the expansion cavity; for example, 1 to 15 seconds, then the test device placed in an incubator for a time period, then removed and the test results observed or measured.
The test device and method will be described for the purposes of illustration only in connection with certain embodiments; however, it is recognized that various changes, additions, improvements and modifications to the illustrated embodiments may be made by those persons skilled in the art, all falling within the spirit and scope of the invention.